| 論文種別 | 原著(症例報告除く) |
| 言語種別 | 英語 |
| 査読の有無 | その他(不明) |
| 表題 | Endothelial cell-released CD93 contributes to podocyte injury in idiopathic nephrotic syndrome. |
| 掲載誌名 | 正式名：Science translational medicine 略 称：Sci Transl Med ISSNコード：19466242/19466234 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 18(832),pp.eadw2206 |
| 著者・共著者 | Colin Bauer, Federica Piani, Jonathan Troost, Stefano Da Sacco, Guadalupe Rojas-Sanchez, Pavel Davizon-Castillo, Laura Perin, Ilse Daehn, Md Imtiazul Islam, Audrey Fetsko, Claudia Carrera-Muñoz, Brad Rovin, Xiaolan L Zhang, Mindy Banks, Carmen de Lucas-Collantes, Flor A Ordóñez-Álvarez, Cristina Aparicio-López, Miguel A Lanaspa, Ana Andres-Hernando, Alfons Segarra, Cristina Martinez, Petter Bjornstad, M Scott Lucia, Franz Schaefer, Alev Yilmaz, Aleksandra Zurowska, Xin Wang, Phillip J McCown, Sean Eddy, John Hartman, Laura Mariani, Matthias Kretzler, Yuwen Zhu, Antonia H M Bouts, Elena N Levtchenko, Julie A Dougherty, William E Smoyer, Bryce A Kerlin, Mahmoud Kallash, Danielle E Soranno, José E Cabrera-Sevilla, Juan David Gonzalez-Rodriguez, Bradford J Siegele, Shoji Tsuji, Kazunari Kaneko, Christine B Sethna, Tarak Srivastava, Markus Bitzer, Christopher L O'Connor, Anna Dimberg, Serena Zhao, Liping Yu, Joshua M Thurman, Richard J Johnson, Gabriel Cara-Fuentes |
| 発行年月 | 2026/01 |
| 概要 | Idiopathic nephrotic syndrome (INS) is a podocyte disease triggered by immune-derived factors. Endothelial activation occurs in this context, but whether the activated endothelium contributes to podocyte injury is unknown. We tested the hypothesis that CD93, a protein primarily expressed in the endothelium, is a contributory factor of podocyte injury. We studied 460 patients with INS and 150 with other podocytopathies. CD93 was analyzed in kidney tissue, urine, and serum samples. We tested the efficacy of CD93 blockade in vitro and in vivo and investigated the relationship between soluble CD93 and clinical outcomes in human INS. CD93 was highly expressed by glomerular endothelial cells (GEnCs) in human INS, and INS sera stimulated cultured human GEnCs to release CD93. Mechanistically, soluble CD93 mediated podocyte activation via β1 integrin/FAK signaling in cultured human podocytes. CD93 blockade mitigated the activation of cultured human podocytes and albumin permeability in human GEnC-podocyte cocultures as well as albuminuria, glomerulosclerosis, and podocyte loss in two models of nephrotic syndrome: podocyte-specific transforming growth factor-β1 signaling (PodTgfbr1) mice and adriamycin-treated mice. Cd93 knockout mice showed less proteinuria and glomerulosclerosis, compared with controls, after adriamycin injection. In patients with INS, soluble CD93 was high in urine in ~90% and 50% of patients in relapse and remission, respectively. High urinary CD93 was associated with faster decline in kidney function and slower response to immunosuppression. Soluble and glomerular CD93 was also elevated in other podocytopathies. We conclude that soluble CD93 contributes to podocyte injury. |
| DOI | 10.1126/scitranslmed.adw2206 |
| PMID | 41533775 |